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膀胱癌免疫浸润特征及其临床意义:综合基因组分析。

Profiles of Immune Infiltration in Bladder Cancer and its Clinical Significance: an Integrative Genomic Analysis.

机构信息

Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China.

Key Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, P.R. China.

出版信息

Int J Med Sci. 2020 Mar 5;17(6):762-772. doi: 10.7150/ijms.42151. eCollection 2020.

Abstract

Tumor-infiltrating immune cells are closely related to the prognosis of bladder cancer. Analysis of tumor infiltrating immune cells is usually based on immunohistochemical analysis. Since many immune cell marker proteins are not specific for different immune cells, which may induce misleading or incomplete. CIBERSORT is an algorithm to estimate specific cell types in a mixed cell population using gene expression data. In this study, the CIBERSORT algorithm was used to identify the immune cell infiltration signatures. The gene expression profiles, mutation data, and clinical data were collected from The Cancer Genome Atlas (TCGA) database. Unsupervised consensus clustering was used to acquire the immune cell infiltration subtypes of bladder cancer based on the fractions of 22 immune cell types. Four immune cell clusters with different immune infiltrate and mutation characteristics were identified. In addition, this stratification has a prognostic relevance, with cluster 2 having the best outcome, cluster 1 the worst. These clusters showed distinct mRNA expression patterns. The characteristic genes in subtype cluster 1 were mainly involved in cell division, those in subtype cluster 2 were mainly related in antigen processing and presentation, those in subtype cluster 3 were mainly involved in epidermal cell differentiation, and those in subtype cluster 4 were mainly related in the humoral immune response. These differences may affect the development of the bladder cancer, the sensitivity to treatment as well as the prognosis. Through further validation, this study may contribute to the development of personalized therapy and precision medical treatments.

摘要

肿瘤浸润免疫细胞与膀胱癌的预后密切相关。肿瘤浸润免疫细胞的分析通常基于免疫组织化学分析。由于许多免疫细胞标志物蛋白对不同的免疫细胞并不特异,这可能会导致误导或不完整。CIBERSORT 是一种使用基因表达数据估计混合细胞群体中特定细胞类型的算法。在这项研究中,使用 CIBERSORT 算法来识别免疫细胞浸润特征。从癌症基因组图谱 (TCGA) 数据库中收集基因表达谱、突变数据和临床数据。基于 22 种免疫细胞类型的分数,使用无监督共识聚类来获得膀胱癌的免疫细胞浸润亚型。鉴定出具有不同免疫浸润和突变特征的 4 种免疫细胞簇。此外,这种分层具有预后相关性,簇 2 具有最好的结果,簇 1 最差。这些簇显示出不同的 mRNA 表达模式。亚型簇 1 中的特征基因主要参与细胞分裂,亚型簇 2 中的特征基因主要与抗原加工和呈递有关,亚型簇 3 中的特征基因主要与表皮细胞分化有关,亚型簇 4 中的特征基因主要与体液免疫反应有关。这些差异可能影响膀胱癌的发展、治疗敏感性和预后。通过进一步验证,本研究可能有助于个性化治疗和精准医疗的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d012/7085262/7027cc1eae0b/ijmsv17p0762g001.jpg

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